Transfusion support plays an increasingly prominent role in modern medical care. Blood transfusions are essential not only to save the lives of bleeding trauma victims, but also to the successful outcome of many complex treatments of cancer patients and patients undergoing transplant, cardiac or spine surgery. An estimated 12 million units of blood per year are collected in the United States for transfusion. Many questions remain regarding transfusion biology and medicine. The purpose of this SCOR program to continue to address some of these questions with a group of interrelated, collaborative projects. The areas of emphases in response to the RFA are cytokines, red blood cell transfusion, and immunomodulatory aspects of transfusion. In the area of cytokines, Project 2 proposes to use a novel mouse model developed in the previous grant to study molecular mechanisms of cytokine signaling in megacryocytopoiesis and Project 3 proposes to use gene-knockout mice to study src tyrosine kinases in cytokine signaling in hematopoiesis, In the area of red blood cell transfusions, Project 4 proposes to use the acute isovolemic hemodilution model developed in the previous grant to study the effects of acute anemia on the nervous system, heart and subcutaneous tissue in normal humans. These data will provide a scientific base to determine the indications for red blood cell transfusion. In the area of immunomodulatory aspects of transfusion, Project 6 proposes to study the persistence of donor cells in transfusion recipients and in liver transplant recipients, and Project 7 proposes to study B cells in autoimmunity and in tolerance to platelet alloimmunization. Project 5 was deleted in the last competitive review and Project 1 is being discontinued. The remaining five projects are supported by Administrative Core A and Biostatistics Core B. To grapple with these questions in Transfusion Medicine, we brought together a new multi-disciplinary team in the previous grant. The team has made novel findings and has developed novel experimental systems. In the renewal, we propose to use these novel systems to further study how blood is made and how blood affects different organs in health and disease. The ultimate goals of this program are to make optimal use of blood products, to evaluate and possibly modify the immune effects and understand and possibly stimulate blood production so as to reduce transfusion needs.